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Hepatocellular carcinoma (HCC) is a highly prevalent malignancy and the third highest contributor to cancer-associated deaths globally. Research has increasingly demonstrated a strong correlation between long noncoding RNAs (lncRNAs) and the incidence and progression of HCC. Nonetheless, the exact mechanism whereby the function of lncRNAs in HCC has not been elucidated. This study explored the pathological role of LINC00294 in HCC, as well as the modulatory mechanism involved. Based on the "The Cancer Genome Atlas (TCGA)" database and validation in HCC cell lines and tissues, the expression of LINC00294 was discovered to be upregulated in HCC tissues and correlated with tumor grade and the prognosis of patients with HCC. Functionally, LINC00294 stimulated the proliferation of HCC cells as well as the Warburg effect (aerobic glycolysis) to enhance progression of tumor in vivo. Mechanistically, METTL3/YTHDC1-mediated N6-methyladenosine (m6A) modification underwent a significant enrichment within LINC00294 and was shown to enhance its RNA stability. Moreover, LINC00294 promoted the interaction between YTHDC1 and HK2 and GLUT1 mRNA. Overall, our study illustrates the m6A modification-mediated epigenetic mechanism of LINC00294 expression and regulatory role in HK2and GLUT1 mRNA expression and indicate LINC00294 as a potential biomarker panel for prognostic prediction and treatment in HCC.
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Introduction: The Omicron variant has rapidly spread throughout the world compared to the Delta variant and poses a great threat to global healthcare systems due to its immune evasion and rapid spread. Sex has been identified as a factor significantly associated with COVID-19 mortality, but it remains unclear which clinical indicators could be identified as risk factors in each sex group and which sex-specific risk factors might shape the worse clinical outcome, especially for Omicrons. This study aimed to confirm the relationship between sex and the progression of the Omicron variant and to explore its sex-biased risk factors. Methods: We conducted a retrospective study including 1,132 hospitalized patients with the COVID-19 Omicron variant from 5 December 2022 to 25 January 2023 at Shanghai General Hospital, and the medical history data and clinical index data of the inpatients for possible sex differences were compared and analyzed. Then, a sex-specific Lasso regression was performed to select the variables significantly associated with critical illness, including intensive care unit admission, invasive mechanical ventilation, or death. A logistic regression was used to construct a sex-specific predictive model distinctively for the critical illness outcome using selected covariates. Results: Among the collected 115 clinical indicators, up to 72 showed significant sex differences, including the difference in merit and the proportion of people with abnormalities. More importantly, males had greater critical illness (28.4% vs. 19.9%) and a significantly higher intensive care unit occupancy (20.96% vs. 14.49%) and mortality (13.2% vs. 4.9%), and males over 80 showed worse outcomes than females. Predictive models (AUC: 0.861 for males and 0.898 for females) showed 12 risk factors for males and 10 for females. Through a comprehensive sex-stratified analysis of a large cohort of hospitalized Omicron-infected patients, we identified the specific risk factors for critical illness by developing prediction models. Discussion: Sex disparities and the identified risk factors should be considered, especially in the personalized prevention and treatment of the COVID-19 Omicron variant.
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BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is clinically dominant and accounts for ~ 80% deaths in all types of ovarian cancer. The delayed diagnosis, rapid development, and wide dissemination of HGSOC collectively contribute to its high mortality rate and poor prognosis in the patients. Suppressors of cytokine signaling 7 (SOCS7) can regulate cytokine signaling and participate in cell cycle arrest and regulation of cell proliferation, which might also be involved in carcinogenesis. Here, we designated to investigate the functions and mechanisms of SOCS7 in HGSOC. METHODS: The clinical correlation between SOCS7 and HGSOC was examined by both bioinformatics and analysis of tissue samples in patients. Gain/Loss-of-function examinations were carried out to assess the effectiveness of SOCS7 in cell viability, cell cycle, and tumor growth of HGSOC. Furthermore, the underlying mechanisms were explored by identifying the downstream proteins and their interactions via proteomics analysis and immunoprecipitation. RESULTS: The expression of SOCS7, which was decreased in HGSOC tissues, was correlated with the clinical pathologic characteristics and overall survival of HGSOC patients. SOCS7 acted as a HGSOC suppressor by inhibiting cancer cell viability and tumor growth in vivo. The anti-HGSOC mechanism involves SOCS7's regulatory effect on HuR by mediating its ubiquitination, the regulation of FOXM1 mRNA by HuR, as well as the interplays among these three clinically relevant factors. CONCLUSIONS: The SOCS7 correlates with HGSOC and suppresses its tumorigenesis through regulating HuR and FOXM1, which also suggests that SOCS7 is a prospective biomarker for the clinical management of ovarian cancer, especially HGSOC.
